1. Field of the Invention
The present invention relates to a process for the synthesis of a xcex2-amino acid by enantioselective catalytic hydrogenation of a prochiral N-acetylated xcex2-aminoacrylic acid.
2. Discussion of the Background
Because of their structural similarity to a-amino acids, xcex2-amino acids may exhibit quasi-analogous behavior. Thus, intensive research in the chemical and pharmaceutical industry has been focused on xcex2-amino acids with the aim to synthesize new bioactive agents with improved characteristics. One of the areas receiving attention is the enantioselective synthesis of xcex2-amino acids.
In a recently published article (J. Org. Chem. 1999, 64, 6907), Zhang et al. describe the enantioselective catalytic hydrogenation of N-acylated xcex2-aminoacrylic acids with rhodium catalysts carrying chiral ligands such as BICP and MeDuPHOS. The significance of the teaching by Zhang et al. is that relatively high hydrogen pressures and nonpolar aprotic solvents, among other factors, appear to be most favorable for the enantioselective catalytic hydrogenation. Furthermore, only the Rh-BICP complex yields high enantiomeric excesses for the corresponding Z-isomer at high pressures close to 20 bar, whereas the Rh-MeDuPHOS catalyst achieves only moderate to poor values.
Noyori et al. have also performed corresponding hydrogenation experiments (Tetrahedron: Asymmetry 1991, 2, 543554), albeit with less favorable results.
It is therefore an object of the present invention to provide a process for the synthesis of a xcex2-amino acid that is readily applicable on an industrial scale and therefore superior to the known processes, particularly from the economic and ecological viewpoints.
It is another object of the present invention to provide a process for the synthesis of a xcex2-amino acid that proceeds at a low hydrogen pressure and shorter hydrogenation times than known processes.
This and other objects have been achieved by the present invention the first embodiment which includes a process for synthesis of an enantiomerically enriched N-acylated xcex2-amino acid, comprising:
enantioselectively catalytically hydrogenating a prochiral N-acylated xcex2-aminoacrylic acid in a polar solvent;
wherein said by hydrogenating is carried out in the presence of a compound of formula (I) 
wherein
each of R1, R2, R3, R4 independently of one another represents C1-C8)-alkyl, (C2-C8)-alkoxyalkyl, (C6-C18)-aryl, (C7-C19)-aralkyl, (C3-C3-C18)-heteroaryl, (C4-C19)-heteroaralkyl, (C1-C8)-alkyl-(C6-C18)-aryl, (C1-C8)-alkyl-(C3-C18)-heteroaryl, (C3-C8)-cycloalkyl, (C1-C8)-alkyl-(C3-C8)-cycloalkyl or (C3-C8)-cycloalkyl-(C1-C8)-alkyl; and
A represents a (C2-C5)-alkylene bridge, a 1,2-(C3-C8)-cycloalkylene bridge or a 1,3-(C3-C8)-cycloalkylene bridge, which can contain one or more double bonds and/or can be substituted with one or more (C1-C8)-alkyl, (C1-C8)-aryl, (C1-C8)-alkoxy, (C2-C8)-alkoxyalkyl, (C6-C18)-aryl or (C3-C3)-cycloalkyl and/or can contain a hetero atom selected form the group consisting of N, O, P and S in said aryl ring;
with the proviso that A is not permitted to be a 2,2xe2x80x2-(1,1xe2x80x2-binaphthylene) group.